期刊
CELL
卷 163, 期 1, 页码 134-147出版社
CELL PRESS
DOI: 10.1016/j.cell.2015.08.040
关键词
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资金
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)
- NHMRC Early Career Fellowship
- NWO ZonMW-TOP
- STW grant [12150]
- ERC [AdG 294325-GeneNoiseControl]
- NWO VICI Award
- NIH [R01 GM114190]
- National Human Genome Research Institute grant [R01 HG003143]
- European Research Council (ERC) [AdG 293662-CHROMATINPRINCIPLES]
Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization.
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